Joint disorders and injuries are widespread, can cause considerable discomfort, and cost billions of dollars in lost days of work. Symptoms of these diseases and injuries include inflammation, lameness, loss of mobility, and pain.
Arthritis is a multifactorial degenerative joint disease, which progresses with age and results in joint stiffness, inflammation, and pain. A joint is formed where two bones meet. The healthy joint bones are lined with spongy cartilage which act as shock absorbers, and the synovial fluid, which is secreted by the synovial membrane lining the joint space, acts as a lubricant that prevents friction. There are two major types of arthritis, osteoarthritis, and rheumatoid arthritis.
Osteoarthritis is a condition occurring due to the progressive degeneration and the wearing away of the cartilage (the cushion between the joints), especially at the large joints like the hips and knees. It is a normal age-related degenerative process, occurring gradually after normal wear and tear. Being overweight, inheriting the wrong genes, or simply growing old can make the problem worse. Almost 80% of the people over the age of 60 years, all over the world, suffer from this disorder. OA begins with the breakdown of cartilage resulting in pain, inflammation, and progressive stiffness in the joint. Joint strengthening through exercise, weight maintenance, and non-steroidal anti-inflammatory drugs (NSAIDs) can alleviate symptoms. Osteoarthritis is often accompanied by osteoporosis, a condition where the bone calcium resorption occurs due to hormonal imbalance, making the bone more brittle, which may lead to frequent fractures.
Rheumatoid arthritis is a prostaglandin-mediated joint disease that leads to irreversible crippling of small joints, especially the fingers and toes. This condition is difficult to handle and only prostaglandin synthetase inhibitors can give some relief to patients. Essentially, the body's immune system attacks the cartilage, and the white blood cells (leukocytes) attack the collagen. Statin drugs, which are immunomodulators, are used frequently, though they have serious side effects. Temporary relief may be obtained from NSAIDs. However, overuse of these drugs can lead to ulcers.
Soft tissue rheumatism is a condition where many parts of the body can be affected for a variety of reasons. In many instances, soft tissue rheumatism is a sport-induced injury, such as a sprain, tennis elbow, or runner's knee. Soft tissues are the ligaments, tendons, and tendon sheath. Ligaments are bands of tissue that connect bones. Tendons are bands of tissue that connect muscle to bone. The tendon sheath is the tissue that surrounds and lubricates the tendon. Injury to any of these soft tissues can produce inflammation, pain, and stiffness. These conditions typically clear up quickly, within several days to weeks, and are usually treated with NSAIDs, icing the affected area, and rest. Nevertheless, expedited recovery is still desirable, as these injuries can cause considerable discomfort and reduce workplace productivity.
In addition to the use of NSAIDs, the inflammatory response can be regulated through the use multiple other drugs (see, Goodman & Gilman's “The Pharmacological Basis of Therapeutics” eds. Hardman et al. Ninth Edition, McGraw-Hill Publishing, 1996). Unfortunately, certain anti-inflammatory drugs presently available produce cytotoxic effects that reflect their initial employment as cancer chemotherapeutics, typically anti-neoplastics. For example, corticosteroids, which are often used for treatment of acute inflammation, manifest significant adverse effects, such as inducing Cushingoid features, skin thinning, increased susceptibility to infection, and suppression of the hypothalamic-pituitary-adrenal axis.
Joint injuries and conditions as described above also afflict numerous other mammals, including domesticated animals such as dogs, cats, and horses. In particular, horses often sustain considerable joint injuries due to their participation in sporting events or use for farm work. Lameness due to traumatic joint disease is a common clinical problem in horses and is one of the most important sources of financial losses in the equine industry.
In recent years NSAIDS (non-steroidal anti-inflammatory drugs), such as phenylbutazone, have been used to eliminate, diminish, or at least assist in managing the lameness in performance horses in all aspects of the horse industry (including racing, cutting, reigning, hunter-jumper, dressage, rodeo, barrel-racing). Unfortunately, NSAIDS require prescriptions and/or veterinary dispensing, are costly, and are accompanied by mild severe, and sometimes even catastrophic side effects.
As described previously, such methods for treatment of both humans and animals only allow temporary relief and/or exhibit side effects from prolonged use. Therefore, there is a need for safe and effective treatment which can be used on a long-term basis without side effects and which also promotes rebuilding of the injured/diseased joints. The present invention fulfills this and other needs.